Prevalence of iodine deficiency and goitre during pregnancy in east ...

European Journal of Endocrinology (2000) 143 479±483

ISSN 0804-4643

CLINICAL STUDY

Prevalence of iodine de®ciency and goitre during pregnancy in east Hungary E Mezosi, I Molnar3, A Jakab4, E Balogh1, Z Karanyi, Z Pakozdy1, P Nagy1, F Gyory2, J Szabo, L Bajnok, A Leovey, G Kakuk and E V Nagy 1st Department of Medicine, 1Department of Radiology and 21st Department of Surgery, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary, 33rd Department of Medicine, Kenezy County Hospital, Debrecen, Hungary and 4Health Care System, Debrecen, Hungary (Correspondence should be addressed to E V Nagy, 1st Department of Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, PO Box 19, H-4012, Hungary)

Abstract Objective: To assess the iodine nutritional status and the prevalence of goitre during pregnancy in a region of Hungary that appeared to be iodine suf®cient in previous studies. Design: A cross-sectional voluntary screening study was organized in which 313 pregnant women participated. Methods: Urine iodine concentration and the volume of the thyroid gland were measured in every woman. In the presence of low urinary iodine concentrations, goitre, or both, thyroid function tests were performed. Results: Iodine de®ciency was found in 57.1% of the pregnant women, and was severe in 15.6%. The volume of the thyroid gland was enlarged in 19.2% of individuals. Nodular goitre was found in 17 women (5.4%). The frequency of goitre and the mean thyroid volume were increased in the group of iodine-de®cient women. In the 89 cases of iodine de®ciency or goitre, thyrotrophin concentrations were in the normal range; however, the free triiodothyronine:free throxine ratio was increased in 97% of them, indicating that the thyroid gland was in a stimulated state in these individuals. Conclusions: Iodine de®ciency with high prevalence of goitre was recognized among pregnant women in an area that previously appeared to be iodine suf®cient. An unexpected mild iodine de®ciency was also noted in the non-pregnant control group. Reassessment and continuous monitoring of iodine nutritional status is warranted even in populations that are apparently considered to be `at no risk' of iodine de®ciency, especially in pregnant women. Regular administration of iodine, starting at preconception or in early pregnancy and continuing during the period of nursing, is recommended in these regions. European Journal of Endocrinology 143 479±483

Introduction Iodine supply is inadequate in most parts of Hungary, except in small areas of the Great Plains (1±4). Several attempts have been made to eliminate this iodine de®ciency (5). Since the 1970s, the issue of inadequate iodine intake has been publicized by several authors as a problem requiring immediate attention (1±3). Iodized salt and iodine-containing tablets can be purchased on a voluntary basis; however, as no state-organized program has been developed, inadequate iodine intake has remained a nation-wide health problem. Previous studies found the region of Debrecen (which is situated on the Great Plains) to be an area of adequate iodine intake as judged by the low frequency of goitre in the population, except for a few clusters of small villages (4±6). q 2000 Society of the European Journal of Endocrinology

Previous investigations con®rmed that the most detrimental effects of inadequate nutritional iodine intake appear in pregnant women and in children (7±9). Hormonal changes and metabolic demands during pregnancy result in alterations in the biochemical parameters of thyroid function (10). The effects of iodine de®ciency become manifest even in geographical areas of borderline iodine supply, because the thyroid gland cannot meet the demand for increased production of thyroid hormone (10±13). The main changes in thyroid metabolism in pregnancy are well characterized (10±15). Iodine de®ciency triggers compensatory stimulating events affecting the thyroid gland of both the mother and the fetus. With respect to long-term effects, the development of goitre is only of secondary importance; the detrimental effect of mild thyroid insuf®ciency (de®ned by a moderate decrease in Online version via http://www.eje.org

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maternal free thyroxine (FT4) concentration) on the neuropsychological development of the child has been repeatedly emphasized (9, 16±22). We assumed that, in a community with apparently suf®cient iodine intake, the increased iodine demand during pregnancy might lead to manifest iodine de®ciency in pregnant women. In the present study we show that the iodine nutritional status found in the general population may not reliably re¯ect the iodine supply of pregnant women living in the same region.

Participants and methods Participants We enrolled 313 pregnant women into a cross-sectional voluntary screening study, which was coordinated by the physicians and nurses of the Health Care System in Debrecen. The ages of the women were 26.8 6 5.2 (range 17±47) years and the gestational ages were 23.6 6 7.9 (6±39) weeks. Multivitamin products, which may contain iodine, are routinely offered to pregnant women by gynaecologists. The consumption of these drugs and the use of iodized salt were elicited by detailed history and four groups were established according to the form of iodine supplementation: group A, no iodine supplementation (n 119); group B, regular use of iodized salt, no consumption of iodinecontaining multivitamins (n 50); group C, taking iodine-containing multivitamins, no use of iodized salt (n 91); group D, regular use of iodized salt and iodine-containing multivitamin tablets (n 53). Overall, 46% of women consumed iodine-containing multivitamin products. The gestation times of those in the nonmultivitamin consuming groups (A and B: 24.6 6 8.1 weeks) and the multivitamin consuming groups (C and D: 23.9 6 7.4 weeks) did not differ signi®cantly. To assess the iodine supply in the general population, samples from 220 non-pregnant women were also analysed.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143

separately by measuring the three main diameters, and the total volume of the thyroid was calculated by the algorithm p/6 ´ height ´ width ´ depth. The upper limit of normal thyroid volume was 18 ml. In cases of urinary iodine less than 50 mg/g creatinine or diffuse or nodular goitre, further tests were offered to the expectant mothers; 89 of them were willing to continue the investigations. Thyroid-stimulating hormone (TSH) was assayed by a third-generation immunochemiluminometric assay and FT4 by a competitive-binding, one-step chemiluminescent immunoassay (both from Byk-Sangtec Diagnostica Gmbh & Co., Dietzenbach, Germany). Free tri-iodothyronine (FT3) was assayed by a two-step saturationcompetitive binding microparticulate enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA).

Data analysis The relationship between thyroid volume and iodine excretion was analysed statistically using ANOVA, and groups were compared using the Newman±Keuls test. The median test and the Pearson x2 - test were applied to analyse the effect of iodine supplementation on urinary iodine excretion. The level of signi®cance in all statistical tests was set at P # 0.05.

Results Urinary iodine excretion Iodine de®ciency among pregnant women in the city of Debrecen was much more frequent than we had

Methods Urine iodine concentration was determined from the ®rst morning urine void, by the Sandell±Kolthoff colourimetric method (23). The iodine concentration of the urine was standardized against that of creatinine, urine creatinine concentrations being measured on the days of sampling. Urine specimens were stored at 208C until required for analysis. The iodine de®ciency was regarded to be mild with urinary iodine concentration between 50 and 100 mg iodine/g creatinine, moderate in the range 25±50 mg iodine/g creatinine and severe when values were less than 25 mg iodine/g creatinine. Thyroid volume measurements were performed by ultrasound (Siemens Sonoline SL-1, 7.5 MHz linear transducer). Each lobe of the thyroid gland was assessed www.eje.org

Figure 1 Urinary iodine concentrations in 313 pregnant women living in Debrecen. Severe iodine de®ciency (urinary iodine 0±25 mg/g creatinine) was detected in 15.6% of the women, moderate de®ciency (25±50 mg iodine/g creatinine) in 15.9% and mild de®ciency (50±100 mg iodine/g creatinine) in 25.6%. The urinary iodine excretion was normal (> 100 mg iodine/g creatinine) in 42.9% of these pregnant women.

Iodine de®ciency in pregnancy


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Figure 2 Urinary iodine excretion in women grouped according to their iodine supplementation. Group A: no iodine supplementation; group B: regular use of iodized salt; group C: consumption of iodinecontaining multivitamins, no use of iodized salt; group D: regular use of iodine-containing multivitamins and iodized salt. Data are presented as median+upper quartile. The median urinary iodine excretion was signi®cantly lower in groups A and B than in groups C and D (*P < 0.01). The use of iodized salt did not in¯uence the urinary iodine concentrations. No signi®cant difference was found between groups C and D.

expected before the study (Fig. 1): normal urine iodine concentration was measured only in 42.9% of the women. The level of iodine de®ciency was mild in 25.6%, moderate in 15.9% and severe in 15.6% of pregnant women. The median urinary iodine excretion was 57, 68, 130 and 115 mg/g creatinine in groups A, B, C and D respectively (Fig. 2); that in the control group of 220 non-pregnant woman was 82 mg iodine/g creatinine. The regular use of iodized salt did not in¯uence the median urinary iodine excretion, but the consumption of multivitamin drug products increased the urinary iodine concentrations signi®cantly. No signi®cant difference in the median urinary iodine excretion was found between groups C and D (consumption of iodine-containing multivitamins respectively without and with iodized salt), therefore we combined the results of groups A and B, and those of groups C and D in further analyses. Although the frequency of iodine de®ciency was lower in women

taking iodine-containing multivitamins than in those without iodine supplementation, adequate iodine intake was measured only in 55% of women who were taking regular multivitamin iodine supplementation (Fig. 3). Iodine de®ciency was diagnosed in 69% of expectant mothers without iodine-containing multivitamin consumption, and in 45% taking iodinecontaining multivitamins.

Maternal thyroid ultrasound The volume of the thyroid gland was in excess of the normal value of 18 ml in 19.2% of the women. Nodular goitre was diagnosed in 17 (5.4%). The mean thyroid volume of women with severe iodine de®ciency was signi®cantly larger than that in the group with adequate iodine intake, and the frequency of goitre was increased in all groups with iodine de®ciency (Fig. 4).

Maternal thyroid parameters In 89 women with low urine iodine excretion or goitre, further thyroid tests were performed. The mean TSH was 1.11 6 0.54 mIU/l, which is within the normal range of 0.3±3.0 mIU/l. However, the FT3:FT4 ratio was remarkably increased at 0.45 6 0.13, and was above the upper limit of normal (0.25) in 97% of the women.

Discussion Figure 3 The distribution of urinary iodine concentrations separately among pregnant women who were (open bars, n 144) or were not (solid bars, n 169) consuming iodine-containing multivitamins (150 mg/day). The prevalence of low urinary iodine excretion was signi®cantly greater in the latter group (P < 0.01). Even with iodine replacement, only 55% of the women were iodine suf®cient.

Considering that previous studies have concluded that the region of Debrecen was an area of suf®cient iodine supply (1, 2, 4, 5), it is striking that, on the basis of urinary iodine excretion, we found mild iodine de®ciency in the non-pregnant female population. More importantly, 57.1% of pregnant women in Debrecen were found to be iodine de®cient and 19.2% had goitre. One possible explanation is a change in available iodine www.eje.org

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Figure 4 Frequency of goitre (open bars) and mean thyroid volume (solid bars) in relation to the urinary iodine concentration in pregnant women. Signi®cant thyroid enlargement was found in those with severe iodine de®ciency (*P 0.01). The frequency of goitre was increased in all groups with iodine de®ciency (P < 0.01).

in this area. A decrease in iodine intake in the past 15 years has also been observed in the USA, resulting in low urinary iodine concentrations in 15% of women of childbearing age (24). In Hungary, where both iodized and non-iodized salts are available, iodized salt is not used during the industrial production of foodstuffs, and usually only a small part of a meal is prepared at home. In our study, the regular use of iodized salt at home before and during pregnancy did not result in an improvement in iodine nutritional status, as urinary iodine excretion in women supplementing their iodine intake did not differ signi®cantly from that in women not taking any form of iodine replacement. Among pregnant women receiving no iodine supplementation or using only iodized salt at home, the prevalence of iodine de®ciency was 69%. Nearly 50% of pregnant women involved in this study received iodine supplementation in the form of multivitamin tablets containing 150 mg iodine, taken once a day. These products were offered as part of the routine obstetric regimen, and not with the speci®c purpose of counteracting iodine de®ciency (as iodine de®ciency had not been suspected). Even in pregnant women receiving this form of iodine supplementation, urinary iodine excretion was suf®cient in only 55%. The reason for this may be multifold. The recent WHO recommendation is for the daily nutritional intake of 200 mg iodine during pregnancy and lactation (13). However, in goitre-endemic regions we would expect to encounter decreased iodine concentrations in the thyroid at the beginning of pregnancy (11). In such cases, favourable results are more likely to be achieved with 300±400 mg daily iodine. Compliance with the drug therapy is also an important factor. Finally, exact data are not available concerning the pharmacokinetic properties of the iodine-containing drug products. Our results demonstrated that occasional iodine supplementation in the form of multivitamins prescribed by gynaecologists www.eje.org


was not adequate across the pregnant population as a whole. Conscious iodine supplementation therapy is necessary, with regular control of the compliance of women. The urinary iodine excretion and the frequency of goitre in pregnant women in Debrecen were similar to those found by studies examining large populations around Brussels and in the southwest of France, which are marginally iodine-de®cient regions (11, 25). These results indicate that a general survey of iodine nutritional status in pregnancy is recommended even in regions that are presumed to be iodine suf®cient. The causative role of iodine de®ciency underlying the high frequency of goitre was strongly supported by the facts that the thyroid volume and the frequency of goitre were signi®cantly larger in women with iodine de®ciency than in the group with adequate iodine intake. As there are no methods available to estimate intrathyroid iodine pools on an individual basis, biochemical markers such as increased FT3 : FT4 ratio, decreased FT4, increased thyroglobulin concentration and increased thyroid gland volume are useful surrogate tools (10±13). The FT3 : FT4 ratio was increased in 97% of iodine-de®cient women. This can be interpreted as the result of the pathological stimulation of the thyroid gland by iodine de®ciency. The association of low FT4 with a normal TSH value seems to be typical for iodine-de®cient pregnancies. In late pregnancies, decreased FT4 concentrations with normal TSH were found in 17% and 33% of women in the southwest of France and in Belgium, respectively (11, 25). The exact cause of this phenomenon is not clearly understood. One explanation is that the determination of free hormones is in¯uenced by the high serum concentration of thyroxin-binding globulin, resulting in false-positive low FT4 concentrations (26). Others concluded that iodine-de®cient pregnant women suffered from true hypothyroxinaemia (14). The latter theory is supported by the fact that, in a region of adequate iodine intake, the prevalence of low FT4 concentration was only 0.3% (27). In conclusion, in the area of Debrecen, which previously appeared to be iodine suf®cient, 57.1% of the pregnant women suffered from iodine de®ciency and 19.2% had goitre. An unexpected mild iodine de®ciency was also noted in the non-pregnant control group. The home usage of iodized salt does not seem to improve appropriately the iodine nutritional status in pregnancy, and occasional iodine supplementation in the form of multivitamin tablets resulted in partial success. Reassessment and continuous monitoring of iodine nutritional status in pregnancy is warranted even in populations that are apparently considered to be `at no risk' of iodine de®ciency. Regular administration of iodine, starting at preconception or in early pregnancy and continuing during the period of nursing, is recommended in these regions.

Iodine de®ciency in pregnancy


Acknowledgements The authors are grateful to Merck KG & A for providing the mobile ultrasound unit, which was used throughout the study.

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